Detailed studies of the intracellular distribution and metabolism of estrogens in human endometrium will be continued. These investigations will include the evaluation of changes during the menstrual cycle of enzymatic activities related to metabolism and formation of estradiol from circulating precursors, and of endogenous concentrations of endomentrial estradiol and estrone. The nuclear binding of hormones (e.g., estradiol in endometrium) will be examined in regard to the homogeneity of low capacity, high affinity sites, using differential salt extraction procedures and sequential labeling with radioactivity competitors. Inductive effects of progesterone on enzymatic systems acting on hormones at the target tissue level will be investigated. Previous work has revealed the potential physiologic and therapeutic significance of progesterone action on the endometrial estradiol dehydrogenase. The proposed studies will involve 2-3 day incubations of human tissue in culture medium containing progesterone, with proper controls. In vivo experiments will require oral administration of Provera for 3-4 days before surgical removal of tissue (endometrium, breast cancer metastases) for reasons unrelated to these studies. Among the enzymatic activities to be studied are the 17beta and the 3alpha dehydrogenases, which are of importance in the regulation of the levels of estradiol in endometrial and mammary tissue and of testosterone and 5alpha dihydrotestosterone in prostate and seminiferous tubules. The regulation by progestins of hormone receptor levels in target tissue will also be studied during these experiments. The influence of estrogens on progesterone receptors and progesterone-induced estradiol dehydrogenase in endometrium will be investigated by administering ethynylestradiol orally to patients during the secretory phase of their menstrual cycle.